Trial reportInvestigational new drugs2014
Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study.
Trial report in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed.
- Novel aldo-keto reductase 1C3 inhibitor affects androgen metabolism but not ovarian function in healthy women: a phase 1 study.European journal of endocrinology · 2023Trial
- Cancer-Associated Fibroblasts in Prostate Cancer: Unraveling Mechanisms and Therapeutic Implications.Oncology research · 2026Review
- LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.Cancer research · 2024Article
- AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications.ACS medicinal chemistry letters · 2024Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Targeting sex steroid biosynthesis for breast and prostate cancer therapy.Nature reviews. Cancer · 2023Review
- AKR1C3 Converts Castrate and Post-Abiraterone DHEA-S into Testosterone to Stimulate Growth of Prostate Cancer Cells via 5-Androstene-3β,17β-Diol.Cancer research communications · 2023Article
- Aldo-Keto Reductase 1C3 Inhibitor Prodrug Improves Pharmacokinetic Profile and Demonstrates In Vivo Efficacy in a Prostate Cancer Xenograft Model.Journal of medicinal chemistry · 2023Article
- In Silico and In Vitro Assessment of Carbonyl Reductase 1 Inhibition Using ASP9521-A Potent Aldo-Keto Reductase 1C3 Inhibitor with the Potential to Support Anticancer Therapy Using Anthracycline Antibiotics.Molecules (Basel, Switzerland) · 2023Article
- Polycystic ovary syndrome: pathophysiology and therapeutic opportunities.BMJ medicine · 2023Review
- Computational modeling studies reveal the origin of the binding preference of 3-(3,4-di hydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over its isoforms.Protein science : a publication of the Protein Society · 2022Article
- Discovery of Novel Aldo-Keto Reductase 1C3 Inhibitors as Chemotherapeutic Potentiators for Cancer Drug Resistance.ACS medicinal chemistry letters · 2022Article
- Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.Endocrinology · 2022Article
- Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.The Prostate · 2021Article
- Dysregulated androgen synthesis and anti-androgen resistance in advanced prostate cancer.American journal of clinical and experimental urology · 2021Review
- Molecular Phenotyping of AR Signaling for Predicting Targeted Therapy in Castration Resistant Prostate Cancer.Frontiers in oncology · 2021Article
- Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.Journal of medicinal chemistry · 2020Review
- Therapeutic targeting of the androgen receptor (AR) and AR variants in prostate cancer.Asian journal of urology · 2020Review
- Intracrinology-revisited and prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020Review
- Intracrine androgen biosynthesis and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundASP9521 is a first-in-class orally available inhibitor of the enzyme 17 β-hydroxysteroid dehydrogenase type 5 (17 βHSD5; AKR1C3), catalysing the conversion of dehydroepiandrosterone and androstenedione into 5-androstenediol and testosterone. It has demonstrated anti-tumour activity in in vitro and in vivo preclinical models. MATERIAL AND
methodsThis first-in-man phase I/II study utilised a 3 + 3 dose escalation design starting at 30 mg ASP9521/day, with the aim of defining a maximum tolerated dose, as defined by the incidence of dose-limiting toxicities. Eligible patients received ASP9521 orally for 12 weeks. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics and anti-tumour activity were assessed.
resultsThirteen patients (median age: 68 years; range 52-76) with metastatic castration-resistant prostate cancer (mCRPC) progressing after chemotherapy were included; 12 patients discontinued treatment at or before week 13, mainly due to disease progression. The most common adverse events were grade 1/2 and included asthenia (N = 5), constipation (N = 4), diarrhoea (N = 3), back pain (N = 3) and cancer pain (N = 3). PK demonstrated a half-life (t1/2) ranging from 16 to 35 h, rapid absorption and dose proportionality. No biochemical or radiological responses were identified; neither endocrine biomarker levels nor circulating tumour cell counts were altered by ASP9521. Given the lack of observable clinical activity, the study was terminated without implementing a planned 12-week dose expansion part at selected doses or a planned food-effect study part.
conclusionsIn patients with mCRPC, ASP9521 demonstrated dose-proportional increase in exposure over the doses evaluated, with an acceptable safety and tolerability profile. However, the novel androgen biosynthesis inhibitor showed no relevant evidence of clinical activity.
Indexed as
Identifiers
24771350What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.